Биологическая активность
ABBV-744 is a BDII-селективный BET bromodomain ингибитор that is being investigated to treat AML and metastic castration-resistant prostate cancer.BBV-744, a highly мощный and селективный ингибитор of the BD2 domain of BET family proteins with препарат-like properties. In contrast to the broad range of клетка growth inhibition induced by DbBi, the antiproliferative activity of ABBV-744 was largely, but not exclusively, restricted to клетка lines of acute myeloid leukaemia and prostate cancer that expressed the full-length androgen рецептор (AR). ABBV-744 retained robust activity in prostate cancer xenografts, and showed fewer platelet and gastrointestinal toxicities than the DbBi ABBV-07514.Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent transcription, with less impact on global transcription compared with ABBV-075. These results underscore the potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy.
Оригинал на английском
ABBV-744 is a BDII-selective BET bromodomain inhibitor that is being investigated to treat AML and metastic castration-resistant prostate cancer.BBV-744, a highly potent and selective inhibitor of the BD2 domain of BET family proteins with drug-like properties. In contrast to the broad range of cell growth inhibition induced by DbBi, the antiproliferative activity of ABBV-744 was largely, but not exclusively, restricted to cell lines of acute myeloid leukaemia and prostate cancer that expressed the full-length androgen receptor (AR). ABBV-744 retained robust activity in prostate cancer xenografts, and showed fewer platelet and gastrointestinal toxicities than the DbBi ABBV-07514.Analyses of RNA expression and chromatin immunoprecipitation followed by sequencing revealed that ABBV-744 displaced BRD4 from AR-containing super-enhancers and inhibited AR-dependent transcription, with less impact on global transcription compared with ABBV-075. These results underscore the potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy.
Химические свойства
- CAS №
- 2138861-99-9
- Брутто-формула
- C₂₈H₃₀FN₃O₄
- Мол. масса
- 491.56 г/моль
- SMILES
- O=C(C(N1)=CC(C(C2=CC(C(C)(O)C)=CC=C2OC3=C(C)C=C(F)C=C3C)=CN4C)=C1C4=O)NCC
- Синонимы
- ABBV-744; ABBV 744; ABBV744；2138861-99-9
3D-структура молекулы
Вращайте мышью · Колесо — масштаб
Хранение и физические свойства
- Условия хранения
- 2 года -20°C порошок, 2 недели 4°C в ДМСО, 6 мес. -80°C в ДМСО
Безопасность и документация
Только для научно-исследовательского применения. Не предназначено для использования у пациентов или в качестве лекарственного средства.